Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants

Mohan Venkatesh and Steven Abrams from Houston, USA are the authors of the review and they set their eligibility criteria to capture randomized trials in babies born before 37 weeks gestation, who were being treated during the first 28 days of their lives. They looked for trials that compared oral lactoferrin at any dose or duration versus placebo or no intervention, where the intention was to prevent sepsis or necrotizing enterocolitis. They were willing to include studies in which a probiotic was combined with the lactoferrin.

The Authors found four trials of the use of lactoferrin in babies, but one of these investigated the use of formula milk supplemented with lactoferrin compared with commercial cow milk-based formula over 12 months, looking at the effect on growth and gastrointestinal, respiratory, and colic illnesses during that year; which meant that it was not eligible.  The results of two other trials could not be included in the review at the moment. One of these started in 2009 and is likely to go on until 2013, and the second completed recently so the results are not yet available. One trial was therefore eligible and available for inclusion in this Cochrane review.

This trial took place in 11 neonatal intensive care units in Italy, during 2007 and 2008. Babies weighing less than 1500 g were allocated to one of three groups: oral bovine lactoferrin, bovine lactoferrin in combination with Lactobacillus rhamnosus GG, or placebo.  A total of 472 babies were randomized, and 29 of the 168 babies in the placebo group developed sepsis, compared to nine of the 153 allocated lactoferrin alone, and seven of the 151 allocated the combination of lactoferrin and the probiotic. The reduction of sepsis by more than two-thirds was statistically significant.

There were also fewer cases of necrotizing enterocolitis in the lactoferrin groups (3 with lactoferrin alone, and none for the combination) compared to the placebo group, in which ten of the babies developed this condition. Fewer of the babies allocated lactoferrin died: four of those in the lactoferrin alone group and six allocated the combination with Lactobacillus rhamnosus GG died, compared to twelve deaths in the placebo group. These differences were not statistically significant.

The effects of lactoferrin on sepsis were most prominent for the subgroup of babies who were under 1000 g at birth. Six of these 53 infants in the lactoferrin group compared to 22 of the 60 in the placebo group were diagnosed with late-onset sepsis. This significant difference is equivalent to a number needed to treat of 4. That is, on average, for every four babies given lactoferrin, sepsis in one infant can be prevented.

Venkatesh and Abrams conclude their Cochrane review by pointing out that questions still remain about the use of lactoferrin in premature babies. They recommend that the short-term findings from the Italian study should be confirmed in new studies and that future research should define optimal dosing, duration and type of lactoferrin. They also suggest that these trials should include long-term follow-up of the babies to assess the effects of lactoferrin on later outcomes, such as neurodevelopment and lung function.